The National NeuroAIDS Tissue Consortium (NNTC) was established in 1998 to advance neuroAIDS research by providing nervous system tissues and fluid samples from persons dying with HIV on whom comprehensive neuromedical, neurocognitive, psychiatric, and laboratory data were gathered during life. The Manhattan HIV Brain Bank (MHBB) is one of 4 founding members of the NNTC. The NNTC has collected antemortem data on 1728 participants and autopsied 721 individuals, distributing samples and data to 212 requests from investigators. While maintaining comprehensive, standardized data and tissue accrual processes and data/sample distribution, the NNTC proposes a restructuring plan to enable development of a consortium-wide scientific agenda. Three levels of scientific activity are envisioned: 1) local preliminary/feasibility studies at NNTC sites, taking advantage of unique expertise; 2) an NNTC-wide internal agenda addressing questions with the consortium's large, unique collection of antemortem and postmortem information; and 3) providing broader leadership for new directions in neuroAIDS research. The MHBB will be uniquely poised to contribute to all levels of resource and scientific activity in the new NNTC. Our cohort, with its large percentage of African American and Hispanic minorities, is representative of the US populations disproportionately impacted by HIV/AIDS. Our large percentage of women and collaboration with the Women's Interagency HIV Study offer an opportunity to evaluate gender-related aspects of nervous system disorders. We have begun, and propose to continue, a series of local pilot analyses to elucidate the impact of co-morbidities and neuroAIDS disparities in the MHBB, which we will advance to the shared NNTC agenda. We have assembled investigators whose expertise is well suited to contribute to the development of internal and broader agendas studying disparities, co-morbidities and peripheral neuropathy. We have supported, and will continue to assist, a variety of neuroAIDS and AIDS investigators by providing tissue samples, and will enhance sample value by performing tissue microarray-based immunohistochemistry to uniformly annotate the NNTC brain collection. The new scientific emphasis and revised structure of the NNTC, with full participation of the MHBB, will enable us to contribute, and be responsive, to rapidly evolving knowledge regarding the neurobiological mechanisms underlying AIDS-related nervous system disorders. Part A: